The long term goal of this project is to understand the molecular basis of the development and differentiation of corneal epithelium. To achieve this goal, we will use a combination of cell culture, biochemical and immunological techniques to investigate four aspects of this complicated problem. Our specific aims for the next five year period are: 1. To study the biochemistry of corneal epithelial differentiation by a) investigating the expression of specific keratin proteins during corneal epithelial differentiation; b) correlating specific keratins with various proliferative states of corneal epithelium; c) comparing the molecular structures of corneal and epidermal keratin filaments; and d) using monoclonal antibodies to further characterize corneal epithelial keratins. 2. To investigate the biochemical basis of xerophthalmia by a) examining the effects of vitamin A deficiency as well as therapy on the expression of the 56K and 65-67K keratins in corneal and conjunctival epithelia; b) developing a non-invasive, sensitive immunoassay for xerophthalmia using monoclonal anti-keratin antibodies; and c) studying xerophthalmia in cell culture. 3. To analyze the embryonic and postnatal development of corneal epithelium by a) defining changes in keratins and other cellular proteins during embryonic development; b) studying the postnatal maturation of rabbit corneal epithelium; and c) determining the developmental relationship between corneal and conjunctival epithelial cells. 4. To study the possible mechanism of posterior polymorphous dystrophy. The work planned embraces several disciplines including morphology, biochemistry and immunology. Data from these experiments should lead to a better understanding of a number of eye diseases including corneal epithelial defects, xerophthalmia, and posterior polymorphous dystrophy.